Why Certain Drug Combinations Backfire

For instance, doctors treat extensively drug resistant forms of tuberculosis with one drug that breaks down the pathogen’s protective barriers and opens the door for another to deliver the deathblow. According to first author and research fellow in systems biology Tobias Bollenbach, clinical researchers are primarily interested in drugs that together work better than either alone, and so studies tend to focus on explaining some of the mechanisms behind synergistic drug pairings. One class of drugs he investigated interrupts the replication of DNA and the other blocks the manufacture of proteins. When the team added the additional stress of a protein-synthesis inhibiting drug, such as Tetracycline, instead of causing the cells more trouble, the second drug counteracted the overproduction of ribosomes and proteins. As a result, the cells could more easily withstand the assault of the first drug, yet succumbed to the second, completely removing the strong antagonism between the drugs. Kishony recently received a federal stimulus grant to pursue a study that explores the genetic determinants of drug interactions more broadly and investigates whether cells can be synthetically manipulated to change the way drugs interact.

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